Total Synthesis of (+)-Haplophytine

摘要

Despite the many impressive accomplishments in the field of total synthesis in recent years, a number of natural products have proven stubbornly resistant to its advances. Among them is haplophytine (1, Scheme 1 a), which has only very recently succumbed to synthesis following the elegant work of Fukuyama, Tokuyama and co-workers. Haplophytine was first isolated by Snyder and co-workers in 1952, and identified as the principle bioactive component of the wild flower Haplophyton cimicidum, valued for centuries by the Aztecs and subsequent settlers of Central America for its insecticidal properties. A heterodimeric indole alkaloid, haplophytine features a particularly complex polycyclic array of ten rings, six stereocenters (five of which are quaternary) and a highly congested carbon-carbon bond adjoining the two distinct halves of the molecule. The tetracyclic left-hand domain features a unique bridged ketone structure, while the right-hand domain consists of the naturally occurring aspidosperma alkaloid, aspidophytine (2, Scheme lb).